What Can Modern Medicine Offer to Patients with Glioblastoma?

When someone receives a diagnosis of glioblastoma multiforme, also called GBM, it often feels like the ground has shifted beneath their feet. This type of brain tumor grows quickly and spreads into surrounding healthy brain tissue, making it extremely difficult to treat. The average person diagnosed with glioblastoma is around 64 years old, though it can appear at any age, and men are diagnosed slightly more often than women.^[1][2]

The central aim of treatment is not just to fight the tumor, but also to help the person live as well as possible for as long as possible. This means managing symptoms like headaches, seizures, weakness, and changes in thinking or personality. Because glioblastoma invades the brain in a way that makes complete removal nearly impossible, treatment strategies focus on removing as much of the tumor as safely possible, then using other therapies to slow down what remains. Every treatment plan is built around the individual patient, taking into account where the tumor is located in the brain, how large it is, the person’s age and general health, and increasingly, the genetic and molecular characteristics of the tumor itself.^[3][8]

The fight against glioblastoma involves multiple types of doctors working together. Neurosurgeons remove the tumor, neuro-oncologists manage drug treatments, radiation oncologists direct radiation therapy, and other specialists provide support for side effects and quality of life. Standard treatments are based on years of research and guidelines published by international medical societies. At the same time, scientists around the world are testing innovative therapies in clinical trials, hoping to find better ways to stop this disease. These trials explore new drugs, advanced technologies, and treatments that target the specific genetic changes found in glioblastoma cells.^[2][10]

Standard Treatment: Surgery, Radiation, and Chemotherapy

The first step in treating glioblastoma is usually surgery. A procedure called a craniotomy is performed, where the surgeon opens the skull to reach the tumor. The goal is to remove as much of the tumor as possible without damaging critical areas of the brain that control movement, speech, sensation, and other vital functions. Complete removal is almost never possible because glioblastoma cells spread like tiny fingers into healthy brain tissue. However, removing the bulk of the tumor can relieve pressure on the brain, reduce symptoms, and improve the effectiveness of treatments that follow.^[8][11]

During surgery, neurosurgeons may use advanced techniques such as intraoperative MRI, which provides real-time images of the brain while the operation is happening, helping the surgeon see exactly how much tumor remains. Some centers also use functional MRI and brain mapping before or during surgery to identify and protect areas responsible for speech, movement, and other important functions.^[1][9]

After the patient recovers from surgery, usually within two to six weeks, the next phase begins: radiation therapy combined with chemotherapy. This combination is known as the standard of care and has been shown to extend survival compared to surgery alone.^[2][10]

Radiation therapy uses high-energy beams, typically X-rays, to kill cancer cells that remain after surgery. The treatment is carefully planned so that the radiation targets the area where the tumor was located, while trying to avoid healthy brain tissue as much as possible. Standard radiation therapy for glioblastoma is usually given five days a week for about six weeks, with each session lasting only a few minutes. The total course involves around 30 treatments, also called fractions. Radiation can cause side effects such as fatigue, temporary hair loss in the treated area, scalp redness, and itching. These effects are generally manageable and tend to improve after treatment ends.^[8][13]

At the same time as radiation, patients begin taking a chemotherapy pill called temozolomide, often known by its brand name Temodar. Temozolomide is the only chemotherapy drug approved specifically for glioblastoma and has been shown to improve survival when given along with radiation. The patient takes the pill once a day, every day, for the entire six weeks of radiation therapy. This is called the concurrent phase.^[10][11]

After the radiation and concurrent chemotherapy are finished, there is a break of about four weeks. Then the patient enters the adjuvant phase, where temozolomide is given at a higher dose for five days in a row, followed by 23 days off. This 28-day cycle is repeated, usually for six cycles, though some patients may continue for up to 12 cycles depending on how they tolerate the treatment and how the tumor responds. Blood tests are done regularly during chemotherapy to monitor blood cell counts, because temozolomide can lower the number of white blood cells, red blood cells, and platelets, which increases the risk of infection, anemia, and bleeding.^[10][13]

The effectiveness of temozolomide depends partly on a specific feature of the tumor called MGMT promoter methylation. Tumors with this feature tend to respond better to temozolomide, and patients with MGMT methylation often live longer than those without it. Doctors can test for this molecular marker in the tumor tissue removed during surgery, and the result helps guide treatment decisions.^[2][10]

In addition to surgery, radiation, and chemotherapy, some patients may benefit from a device called Optune, which delivers tumor-treating fields (TTFields). This is a wearable device that the patient uses at home. It consists of adhesive pads placed on the scalp that deliver low-intensity, alternating electrical fields. These fields interfere with the division of cancer cells, slowing their growth or even destroying them. Optune is approved by the U.S. Food and Drug Administration for adults with newly diagnosed glioblastoma and has been shown to extend survival when used together with temozolomide. Patients wear the device for at least 18 hours a day. The main side effect is skin irritation under the pads.^[13]

Doctors also prescribe medications to manage symptoms and side effects. Corticosteroids, such as dexamethasone, are often given to reduce swelling around the tumor, which can relieve headaches, nausea, and other pressure-related symptoms. However, long-term use of steroids can cause side effects like weight gain, mood changes, high blood sugar, and muscle weakness, so doctors try to lower the dose as soon as possible.^[8][11]

Seizures are common in people with glioblastoma, so anticonvulsant medications may be prescribed to prevent or control them. Not all patients need these drugs, but those who have had a seizure or have a tumor in an area of the brain prone to seizures usually take them.^[1][11]

Despite this intensive treatment, glioblastoma almost always comes back. The median survival time for patients receiving the full standard treatment is about 15 months, though some people live much longer. About 40 percent of patients survive the first year, and around 17 percent reach the second year. Five-year survival is less than 10 percent, which means this disease remains one of the deadliest cancers.^[1][2][10]

Treatment in Clinical Trials: Hope Through Research

Because standard treatment for glioblastoma is not curative, researchers around the world are working intensely to find new therapies. Clinical trials test experimental treatments to see if they are safe and whether they work better than existing options. Many of these trials are focused on targeting the specific genetic and molecular changes that drive glioblastoma, or on helping the immune system recognize and attack the tumor.^[2][10]

Clinical trials are organized into phases. Phase I trials test a new drug or treatment in a small number of patients to see if it is safe and to find the right dose. Phase II trials involve more patients and focus on whether the treatment actually works against the cancer. Phase III trials compare the new treatment to the current standard treatment in a large group of patients to see which one is better. Some centers also conduct Phase 0 trials, which give very small doses of a drug to see how it behaves in the human body and whether it reaches the tumor.^[13][21]

One major area of research is immunotherapy, which trains the patient’s own immune system to fight cancer. Normally, the immune system does not recognize brain tumors as threats, partly because the brain is somewhat isolated from the rest of the body by a barrier of blood vessels called the blood-brain barrier. Researchers are testing several types of immunotherapy for glioblastoma.^[2][10]

Checkpoint inhibitors are drugs that block proteins on immune cells or cancer cells that prevent the immune system from attacking the tumor. Examples include drugs targeting PD-1, PD-L1, and CTLA-4. These drugs have been successful in other cancers like melanoma and lung cancer, and trials are testing whether they can help people with glioblastoma. Early results have been mixed, with some patients responding well while others do not, suggesting that more research is needed to identify which patients are most likely to benefit.^[10]

Cancer vaccines are another form of immunotherapy being studied. These vaccines are designed to teach the immune system to recognize specific proteins found on glioblastoma cells. One approach uses dendritic cells, which are immune cells taken from the patient’s blood, exposed to tumor proteins in the lab, and then injected back into the patient to trigger an immune response. Several dendritic cell vaccine trials are underway in Europe, the United States, and other countries.^[10]

Another exciting area of research involves targeted therapies, which are drugs designed to attack specific molecules involved in cancer growth. Many glioblastomas have changes in genes or proteins that help the tumor grow and survive. For example, a common genetic change is amplification of the EGFR gene, which leads to too much of a protein that tells cells to grow. Researchers have tested drugs that block EGFR, though results so far have been disappointing in clinical trials. However, scientists are developing newer, more effective EGFR inhibitors and testing them in combination with other treatments.^[7][10]

Other molecular targets being explored include VEGF, a protein that helps tumors build new blood vessels. A drug called bevacizumab (Avastin) blocks VEGF and has been approved for recurrent glioblastoma in some countries. Bevacizumab can slow tumor growth and reduce brain swelling, but it does not appear to significantly extend overall survival. It is most often used when glioblastoma comes back after initial treatment.^[4][10]

Some trials are testing drugs called PARP inhibitors, which block an enzyme that cancer cells use to repair their DNA. Glioblastoma cells with certain genetic features may be more vulnerable to PARP inhibitors. One such drug, pamiparib, is being tested in Phase 0 trials at specialized centers. These trials give a small number of patients the drug before surgery, then test the tumor tissue to see if the drug reached the brain and had an effect on the cancer cells.^[21]

Gene therapy is another cutting-edge approach. This involves inserting genetic material into tumor cells to kill them or make them more vulnerable to other treatments. One form of gene therapy uses modified viruses to carry therapeutic genes into cancer cells. Another approach is called oncolytic virotherapy, where viruses are engineered to infect and destroy glioblastoma cells while leaving normal cells alone. Several oncolytic viruses are being tested in clinical trials, and early results show that they are generally safe and may help stimulate an immune response against the tumor.^[4]

Researchers are also exploring nanoparticles and other novel drug delivery systems. Nanoparticles are tiny particles that can carry chemotherapy or other drugs directly to tumor cells, potentially overcoming the blood-brain barrier and reducing side effects on healthy tissue. Some trials are testing nanoparticles loaded with chemotherapy drugs or substances that make cancer cells more visible to the immune system.^[4]

Another innovative treatment being tested is intranasal drug delivery, where drugs are given through the nose to bypass the blood-brain barrier and reach the brain more directly. This method is still experimental but could offer a less invasive way to deliver therapies.^[4]

Clinical trials for glioblastoma are being conducted in many countries, including the United States, Canada, and across Europe. Poland and other European countries participate in international multicenter trials. Patients interested in joining a clinical trial should discuss this option with their doctors. Eligibility depends on many factors, including the patient’s age, overall health, tumor characteristics, and previous treatments. Clinical trials may offer access to treatments that are not yet available outside of research studies, and they contribute valuable knowledge that helps future patients.^[2][13]

Most common treatment methods

• Surgery (Craniotomy)
  • Opening the skull to remove as much of the tumor as possible without damaging critical brain areas.
  • Often guided by intraoperative MRI and brain mapping techniques.
  • Goal is to reduce tumor mass, relieve symptoms, and improve effectiveness of follow-up treatments.
• Radiation Therapy
  • Standard external beam radiation given daily for about six weeks (around 30 sessions).
  • Proton beam therapy, an advanced form, delivers more precise radiation and spares healthy tissue.
  • Gamma Knife radiosurgery may be used for small recurrent tumors.
• Chemotherapy
  • Temozolomide (Temodar) is the main chemotherapy drug, taken as a daily pill during radiation and in cycles afterward.
  • Bevacizumab (Avastin) is used for recurrent glioblastoma to block new blood vessel formation.
  • Other chemotherapy drugs may be tried in clinical trials or when the tumor comes back.
• Tumor-Treating Fields (Optune)
  • A wearable device that delivers low-intensity electrical fields to disrupt cancer cell division.
  • Used at home for at least 18 hours per day in combination with temozolomide.
  • Approved for newly diagnosed glioblastoma and shown to improve survival.
• Immunotherapy
  • Checkpoint inhibitors that help the immune system recognize and attack tumor cells (still in clinical trials for glioblastoma).
  • Cancer vaccines using dendritic cells or tumor-specific proteins to train the immune system.
  • Oncolytic viruses engineered to infect and kill glioblastoma cells.
• Targeted Therapy
  • Drugs that target specific genetic changes in the tumor, such as EGFR amplification or VEGF overexpression.
  • PARP inhibitors that block DNA repair in cancer cells with certain genetic vulnerabilities.
  • Tested mostly in clinical trials; some approved for recurrent disease.
• Supportive Medications
  • Corticosteroids (like dexamethasone) to reduce brain swelling and relieve pressure symptoms.
  • Anticonvulsant drugs to prevent or control seizures.
  • Pain relievers and medications to manage nausea and other side effects.